Oxidative stress and altered lipid homeostasis in the programming of offspring fatty liver by maternal obesity.
Oxidative stress and altered lipid homeostasis in the programming of offspring fatty liver by maternal obesity.
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DOI：
10.1152/ajpregu.00049.2014
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发表时间：
2014-07-01
期刊：
影响因子：
--
通讯作者：
Ozanne SE
中科院分区：
文献类型：
--
作者：
Alfaradhi MZ;Fernandez-Twinn DS;Martin-Gronert MS;Musial B;Fowden A;Ozanne SE
在胎儿发育期间母体营养环境的变化会影响后代在以后生活中的代谢风险。动物模型已经证明，饮食诱导的肥胖母鼠的后代会发生代谢并发症，包括非酒精性脂肪肝。在这项研究中，我们调查了导致非酒精性脂肪性肝病（NAFLD）发展的年轻后代的机制。在8周龄时研究了喂食对照或致肥胖饮食的C57 BL/6 J母鼠的雌性后代。我们研究了氧化应激和脂质代谢在导致后代脂肪肝中的作用。在8周龄时，体重或肥胖没有差异;然而，肥胖母鼠的后代有高胰岛素血症。他们的肝脏氧化损伤标记物显著增加，抗氧化酶谷胱甘肽过氧化物酶-1水平降低。线粒体复合物I和II活性升高，而线粒体细胞色素c水平显着降低，谷氨酸脱氢酶显着增加，表明线粒体功能障碍。肥胖母鼠的后代也具有显著更高的肝脏脂质含量，与PPARγ水平升高和甘油三酯脂肪酶降低相关。在肥胖母鼠的后代中，肝糖原和蛋白质含量同时降低。总之，饮食诱导的肥胖母鼠的后代在体重或身体组成出现任何差异之前就已经破坏了肝脏代谢并发展为NAFLD。氧化应激可能在这些后代脂肪肝的进展中起机械作用。
Changes in the maternal nutritional environment during fetal development can influence offspring's metabolic risk in later life. Animal models have demonstrated that offspring of diet-induced obese dams develop metabolic complications, including nonalcoholic fatty liver disease. In this study we investigated the mechanisms in young offspring that lead to the development of nonalcoholic fatty liver disease (NAFLD). Female offspring of C57BL/6J dams fed either a control or obesogenic diet were studied at 8 wk of age. We investigated the roles of oxidative stress and lipid metabolism in contributing to fatty liver in offspring. There were no differences in body weight or adiposity at 8 wk of age; however, offspring of obese dams were hyperinsulinemic. Oxidative damage markers were significantly increased in their livers, with reduced levels of the antioxidant enzyme glutathione peroxidase-1. Mitochondrial complex I and II activities were elevated, while levels of mitochondrial cytochrome c were significantly reduced and glutamate dehydrogenase was significantly increased, suggesting mitochondrial dysfunction. Offspring of obese dams also had significantly greater hepatic lipid content, associated with increased levels of PPARγ and reduced triglyceride lipase. Liver glycogen and protein content were concomitantly reduced in offspring of obese dams. In conclusion, offspring of diet-induced obese dams have disrupted liver metabolism and develop NAFLD prior to any differences in body weight or body composition. Oxidative stress may play a mechanistic role in the progression of fatty liver in these offspring.
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影响因子：
8.1
作者：
Fernandez-Twinn DS;Alfaradhi MZ;Martin-Gronert MS;Duque-Guimaraes DE;Piekarz A;Ferland-McCollough D;Bushell M;Ozanne SE
通讯作者：
Ozanne SE
影响因子：
8
作者：
Boney, CM;Verma, A;Vohr, BR
通讯作者：
Vohr, BR
影响因子：
7.7
作者：
Marchesini, G;Brizi, M;Melchionda, N
通讯作者：
Melchionda, N
DOI：
10.1111/j.1440-1746.2006.04640.x
发表时间：
2007-06-01
影响因子：
4.1
作者：
Pessayre, Dominique
通讯作者：
Pessayre, Dominique
影响因子：
56.9
作者：
Haemmerle, G;Lass, A;Zechner, R
通讯作者：
Zechner, R